The oral mucosa lining the oral cavity represents a barrier that limits the access of exogenous material to the underlying tissues. Measurements of permeability of the tissue in man and experimental animals indicates that there is considerable variation between different oral regions. Such variation might explain the susceptibility of certain oral regions to disease, where an extrinsic etiology, such as tobacco or alcohol, is involved. A question that arises is whether common pathological conditions of the mucosa such as hyperplasia and hyperkeratosis, which are known to represent a higher risk of malignant disease than unaltered mucosa, are areas of high permeability. The hypotheses underlying the research is that any agent coming in contact with the surface of the oral mucosa must first penetrate the permeability barrier of the epithelium before it can exert a local effect. The specific aim is to determine whether the permeability of human oral mucosa is modified in areas of epithelial alteration, such a hyperplasia and hyperkeratosis. The research will involve the use of methods to measure permeability using specific radiolabeled tracers. Procedures will be modified to permit the use of small (4 mm diameter) biopsies of human oral mucosa. The outcomes will provide important information on the etiology of mucosal disease and will permit investigation of conditions in which increased permeability may be an important etiologic factor.